ID KNL1_HUMAN Reviewed; 2342 AA. AC Q8NG31; Q8NHE1; Q8WXA6; Q9HCK2; Q9NR92; DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 3. DT 27-MAR-2024, entry version 170. DE RecName: Full=Kinetochore scaffold 1; DE AltName: Full=ALL1-fused gene from chromosome 15q14 protein; DE Short=AF15q14; DE AltName: Full=Bub-linking kinetochore protein; DE Short=Blinkin; DE AltName: Full=Cancer susceptibility candidate gene 5 protein; DE AltName: Full=Cancer/testis antigen 29; DE Short=CT29; DE AltName: Full=Kinetochore-null protein 1; DE AltName: Full=Protein CASC5; DE AltName: Full=Protein D40/AF15q14; GN Name=KNL1 {ECO:0000312|HGNC:HGNC:24054}; Synonyms=CASC5, KIAA1570; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), CHROMOSOMAL TRANSLOCATION RP WITH KMT2A/MLL1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANTS RP SER-486; THR-598; GLY-936; GLU-1285 AND ALA-1473. RX PubMed=10980622; DOI=10.1038/sj.onc.1203789; RA Hayette S., Tigaud I., Vanier A., Martel S., Corbo L., Charrin C., RA Beillard E., Deleage G., Magaud J.-P., Rimokh R.; RT "AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid RT leukaemia with a t(11;15)(q23;q14)."; RL Oncogene 19:4446-4450(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND VARIANTS RP THR-43; ALA-113; SER-486; THR-598 AND GLY-936. RC TISSUE=Testis; RX PubMed=12087463; DOI=10.1038/sj.bjc.6600328; RA Takimoto M., Wei G., Dosaka-Akita H., Mao P., Kondo S., Sakuragi N., RA Chiba I., Miura T., Itoh N., Sasao T., Koya R.C., Tsukamoto T., RA Fujimoto S., Kato H., Kuzumaki N.; RT "Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancer RT of smokers."; RL Br. J. Cancer 86:1757-1762(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION WITH RP KMT2A/MLL1, TISSUE SPECIFICITY, AND VARIANTS THR-598 AND GLY-936. RX PubMed=12618768; DOI=10.1038/sj.onc.1206272; RA Kuefer M.U., Chinwalla V., Zeleznik-Le N.J., Behm F.G., Naeve C.W., RA Rakestraw K.M., Mukatira S.T., Raimondi S.C., Morris S.W.; RT "Characterization of the MLL partner gene AF15q14 involved in RT t(11;15)(q23;q14)."; RL Oncogene 22:1418-1424(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 983-2342. RC TISSUE=Brain; RX PubMed=10997877; DOI=10.1093/dnares/7.4.271; RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:273-281(2000). RN [6] RP CHROMOSOMAL TRANSLOCATION WITH KMT2A. RX PubMed=12618766; DOI=10.1038/sj.onc.1206273; RA Chinwalla V., Chien A., Odero M., Neilly M.B., Zeleznik-Le N.J., RA Rowley J.D.; RT "A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene RT MPFYVE on chromosome 15."; RL Oncogene 22:1400-1410(2003). RN [7] RP INTERACTION WITH DSN1 AND MIS12, IDENTIFICATION BY MASS SPECTROMETRY, AND RP FUNCTION. RX PubMed=15502821; DOI=10.1038/ncb1187; RA Obuse C., Iwasaki O., Kiyomitsu T., Goshima G., Toyoda Y., Yanagida M.; RT "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and RT outer kinetochore protein Zwint-1."; RL Nat. Cell Biol. 6:1135-1141(2004). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=15579588; DOI=10.1530/rep.1.00312; RA Sasao T., Itoh N., Takano H., Watanabe S., Wei G., Tsukamoto T., RA Kuzumaki N., Takimoto M.; RT "The protein encoded by cancer/testis gene D40/AF15q14 is localized in RT spermatocytes, acrosomes of spermatids and ejaculated spermatozoa."; RL Reproduction 128:709-716(2004). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BUB1; BUB1B; NSL1; RP DSN1 AND ZWINT. RX PubMed=17981135; DOI=10.1016/j.devcel.2007.09.005; RA Kiyomitsu T., Obuse C., Yanagida M.; RT "Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic RT checkpoint through direct interaction with Bub1 and BubR1."; RL Dev. Cell 13:663-676(2007). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18045986; DOI=10.1091/mbc.e07-10-1051; RA Cheeseman I.M., Hori T., Fukagawa T., Desai A.; RT "KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly RT in vertebrates."; RL Mol. Biol. Cell 19:587-594(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1076, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-60; SER-1076; RP SER-1773 AND SER-1845, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=19450515; DOI=10.1016/j.cell.2009.03.035; RA Wan X., O'Quinn R.P., Pierce H.L., Joglekar A.P., Gall W.E., DeLuca J.G., RA Carroll C.W., Liu S.-T., Yen T.J., McEwen B.F., Stukenberg P.T., Desai A., RA Salmon E.D.; RT "Protein architecture of the human kinetochore microtubule attachment RT site."; RL Cell 137:672-684(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1076, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-539; SER-956; SER-1076 AND RP SER-1831, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-60; THR-539; SER-578; RP SER-584; THR-586; SER-767; SER-956; SER-1039; SER-1076; SER-1088; SER-1448; RP SER-1675; SER-1845 AND SER-1860, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP VARIANT [LARGE SCALE ANALYSIS] THR-598. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). RN [18] RP VARIANT MCPH4 ILE-2041. RX PubMed=22983954; DOI=10.1093/hmg/dds386; RA Genin A., Desir J., Lambert N., Biervliet M., Van Der Aa N., Pierquin G., RA Killian A., Tosi M., Urbina M., Lefort A., Libert F., Pirson I., RA Abramowicz M.; RT "Kinetochore KMN network gene CASC5 mutated in primary microcephaly."; RL Hum. Mol. Genet. 21:5306-5317(2012). RN [19] RP VARIANT MCPH4 ILE-2041. RX PubMed=26626498; DOI=10.1007/s10048-015-0468-7; RA Saadi A., Verny F., Siquier-Pernet K., Bole-Feysot C., Nitschke P., RA Munnich A., Abada-Dendib M., Chaouch M., Abramowicz M., Colleaux L.; RT "Refining the phenotype associated with CASC5 mutation."; RL Neurogenetics 17:71-78(2016). CC -!- FUNCTION: Performs two crucial functions during mitosis: it is CC essential for spindle-assembly checkpoint signaling and for correct CC chromosome alignment. Required for attachment of the kinetochores to CC the spindle microtubules. Directly links BUB1 and BUB1B to CC kinetochores. Part of the MIS12 complex, which may be fundamental for CC kinetochore formation and proper chromosome segregation during mitosis. CC Acts in coordination with CENPK to recruit the NDC80 complex to the CC outer kinetochore. {ECO:0000269|PubMed:15502821, CC ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986}. CC -!- SUBUNIT: Interacts with DSN1, MIS12, BUB1, BUB1B, NSL1 and ZWINT. CC {ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135}. CC -!- INTERACTION: CC Q8NG31; O43683: BUB1; NbExp=2; IntAct=EBI-1001161, EBI-748936; CC Q8NG31; P62136: PPP1CA; NbExp=2; IntAct=EBI-1001161, EBI-357253; CC Q8NG31-2; O43683: BUB1; NbExp=3; IntAct=EBI-10973816, EBI-748936; CC Q8NG31-2; O60566: BUB1B; NbExp=10; IntAct=EBI-10973816, EBI-1001438; CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore. CC Note=Weakly expressed in interphase nuclei. Expression increases from CC prophase to late anaphase, but greatly diminishes from the telophase CC and cytokinesis to early G1 phase of cell cycle. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8NG31-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NG31-2; Sequence=VSP_013795; CC Name=3; CC IsoId=Q8NG31-3; Sequence=VSP_013795, VSP_013796, VSP_013797; CC Name=4; CC IsoId=Q8NG31-4; Sequence=VSP_013795, VSP_018524, VSP_018525; CC -!- TISSUE SPECIFICITY: Highly expressed in testis, where it is localized CC in germ cells, in particular in spermatocytes and in the pre-acrosome CC of round spermatids. Detected in the acrosome of ejaculated CC spermatozoa. Detected in adult thymus, bone marrow, colon, small CC intestine, appendix and placenta, and in fetal liver and thymus. CC {ECO:0000269|PubMed:10980622, ECO:0000269|PubMed:12087463, CC ECO:0000269|PubMed:12618768}. CC -!- DISEASE: Note=A chromosomal aberration involving KNL1 is associated CC with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) CC with KMT2A. May give rise to a KMT2A-KNL1 fusion protein. CC {ECO:0000269|PubMed:12618766}. CC -!- DISEASE: Microcephaly 4, primary, autosomal recessive (MCPH4) CC [MIM:604321]: A disease defined as a head circumference more than 3 CC standard deviations below the age-related mean. Brain weight is CC markedly reduced and the cerebral cortex is disproportionately small. CC Despite this marked reduction in size, the gyral pattern is relatively CC well preserved, with no major abnormality in cortical architecture. CC Affected individuals are mentally retarded. Primary microcephaly is CC further defined by the absence of other syndromic features or CC significant neurological deficits due to degenerative brain disorder. CC {ECO:0000269|PubMed:22983954, ECO:0000269|PubMed:26626498}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/318/AF15q14"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF248041; AAF97513.1; -; mRNA. DR EMBL; AF461041; AAL67803.1; -; mRNA. DR EMBL; AB022190; BAC05691.1; -; mRNA. DR EMBL; AF173994; AAM45143.1; -; mRNA. DR EMBL; AC022405; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB046790; BAB13396.1; -; mRNA. DR CCDS; CCDS42023.1; -. [Q8NG31-1] DR CCDS; CCDS42024.1; -. [Q8NG31-2] DR RefSeq; NP_653091.3; NM_144508.4. [Q8NG31-2] DR RefSeq; NP_733468.3; NM_170589.4. [Q8NG31-1] DR PDB; 3SI5; X-ray; 2.20 A; X/Y=234-252. DR PDB; 4A1G; X-ray; 2.60 A; E/F/G/H=176-226. DR PDB; 4NF9; X-ray; 2.80 A; A/B=2117-2337. DR PDB; 4NFA; X-ray; 2.50 A; A=2131-2337. DR PDBsum; 3SI5; -. DR PDBsum; 4A1G; -. DR PDBsum; 4NF9; -. DR PDBsum; 4NFA; -. DR AlphaFoldDB; Q8NG31; -. DR BMRB; Q8NG31; -. DR EMDB; EMD-2549; -. DR SMR; Q8NG31; -. DR BioGRID; 121354; 125. DR ComplexPortal; CPX-5644; Kinetochore KNL1 complex. DR CORUM; Q8NG31; -. DR DIP; DIP-36474N; -. DR ELM; Q8NG31; -. DR IntAct; Q8NG31; 59. DR MINT; Q8NG31; -. DR STRING; 9606.ENSP00000335463; -. DR GlyCosmos; Q8NG31; 1 site, 1 glycan. DR GlyGen; Q8NG31; 6 sites, 1 O-linked glycan (6 sites). DR iPTMnet; Q8NG31; -. DR PhosphoSitePlus; Q8NG31; -. DR BioMuta; KNL1; -. DR DMDM; 223590239; -. DR CPTAC; CPTAC-5923; -. DR CPTAC; CPTAC-5924; -. DR EPD; Q8NG31; -. DR jPOST; Q8NG31; -. DR MassIVE; Q8NG31; -. DR MaxQB; Q8NG31; -. DR PaxDb; 9606-ENSP00000335463; -. DR PeptideAtlas; Q8NG31; -. DR ProteomicsDB; 73413; -. [Q8NG31-1] DR ProteomicsDB; 73414; -. [Q8NG31-2] DR ProteomicsDB; 73415; -. [Q8NG31-3] DR ProteomicsDB; 73416; -. [Q8NG31-4] DR Pumba; Q8NG31; -. DR ABCD; Q8NG31; 1 sequenced antibody. DR Antibodypedia; 23122; 151 antibodies from 21 providers. DR CPTC; Q8NG31; 1 antibody. DR DNASU; 57082; -. DR Ensembl; ENST00000346991.9; ENSP00000335463.6; ENSG00000137812.21. [Q8NG31-1] DR Ensembl; ENST00000399668.7; ENSP00000382576.3; ENSG00000137812.21. [Q8NG31-2] DR GeneID; 57082; -. DR KEGG; hsa:57082; -. DR MANE-Select; ENST00000399668.7; ENSP00000382576.3; NM_144508.5; NP_653091.3. [Q8NG31-2] DR UCSC; uc010bbs.2; human. [Q8NG31-1] DR AGR; HGNC:24054; -. DR CTD; 57082; -. DR DisGeNET; 57082; -. DR GeneCards; KNL1; -. DR HGNC; HGNC:24054; KNL1. DR HPA; ENSG00000137812; Group enriched (bone marrow, lymphoid tissue, testis). DR MalaCards; KNL1; -. DR MIM; 604321; phenotype. DR MIM; 609173; gene. DR neXtProt; NX_Q8NG31; -. DR OpenTargets; ENSG00000137812; -. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR PharmGKB; PA142672201; -. DR VEuPathDB; HostDB:ENSG00000137812; -. DR eggNOG; ENOG502QW5H; Eukaryota. DR GeneTree; ENSGT00410000025918; -. DR InParanoid; Q8NG31; -. DR OMA; DINRNLW; -. DR OrthoDB; 5354475at2759; -. DR PhylomeDB; Q8NG31; -. DR TreeFam; TF335517; -. DR PathwayCommons; Q8NG31; -. DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal. DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR Reactome; R-HSA-606279; Deposition of new CENPA-containing nucleosomes at the centromere. DR Reactome; R-HSA-68877; Mitotic Prometaphase. DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation. DR SignaLink; Q8NG31; -. DR SIGNOR; Q8NG31; -. DR BioGRID-ORCS; 57082; 605 hits in 1168 CRISPR screens. DR ChiTaRS; KNL1; human. DR EvolutionaryTrace; Q8NG31; -. DR GeneWiki; CASC5; -. DR GenomeRNAi; 57082; -. DR Pharos; Q8NG31; Tbio. DR PRO; PR:Q8NG31; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q8NG31; Protein. DR Bgee; ENSG00000137812; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 130 other cell types or tissues. DR ExpressionAtlas; Q8NG31; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:0180019; C:Knl1/Spc105 complex; IDA:UniProtKB. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001675; P:acrosome assembly; NAS:UniProtKB. DR GO; GO:0008608; P:attachment of spindle microtubules to kinetochore; IDA:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0031619; P:homologous chromosome orientation in meiotic metaphase I; ISS:UniProtKB. DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:UniProtKB. DR GO; GO:1905326; P:positive regulation of meiosis I spindle assembly checkpoint; ISS:UniProtKB. DR GO; GO:0034501; P:protein localization to kinetochore; IDA:MGI. DR GO; GO:0090266; P:regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB. DR CDD; cd21853; KNL1_NTD; 1. DR CDD; cd22892; Knl1_RWD_C; 1. DR CDD; cd22817; Knl1_RWD_N; 1. DR DisProt; DP01269; -. DR IDEAL; IID00417; -. DR InterPro; IPR037388; Blinkin. DR InterPro; IPR043651; KNL1_MELT_rep. DR InterPro; IPR040850; Knl1_RWD_C. DR PANTHER; PTHR16520; KINETOCHORE SCAFFOLD 1; 1. DR PANTHER; PTHR16520:SF3; KINETOCHORE SCAFFOLD 1; 1. DR Pfam; PF18210; Knl1_RWD_C; 1. DR Pfam; PF19221; MELT; 12. DR Genevisible; Q8NG31; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Centromere; KW Chromosomal rearrangement; Chromosome; Chromosome partition; Coiled coil; KW Disease variant; Intellectual disability; Kinetochore; Mitosis; Nucleus; KW Phosphoprotein; Primary microcephaly; Reference proteome; Repeat. FT CHAIN 1..2342 FT /note="Kinetochore scaffold 1" FT /id="PRO_0000089327" FT REPEAT 885..989 FT /note="1" FT REPEAT 1099..1201 FT /note="2" FT REGION 1..728 FT /note="Interaction with BUB1 and BUB1B" FT /evidence="ECO:0000269|PubMed:17981135" FT REGION 1..56 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 620..646 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 855..1201 FT /note="2 X 104 AA approximate repeats" FT REGION 1639..1662 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1834..2316 FT /note="Necessary for kinetochore localization and for FT interaction with NSL1 and DSN1" FT /evidence="ECO:0000269|PubMed:17981135" FT COILED 1942..2133 FT /evidence="ECO:0000255" FT MOTIF 1789..1803 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 632..646 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 1818..1819 FT /note="Breakpoint for translocation to form KMT2A-KNL1" FT /evidence="ECO:0000269|PubMed:12618766" FT MOD_RES 32 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 60 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 539 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 578 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 584 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 586 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 767 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 956 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1039 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1076 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 1088 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1448 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1675 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1773 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1831 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1845 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1860 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 84..109 FT /note="Missing (in isoform 2, isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:10980622, FT ECO:0000303|PubMed:12087463" FT /id="VSP_013795" FT VAR_SEQ 1764..1772 FT /note="LIETYQKEI -> VGTRRRRYS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12087463" FT /id="VSP_013796" FT VAR_SEQ 1773..2342 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12087463" FT /id="VSP_013797" FT VAR_SEQ 1819..1859 FT /note="IFDHHTEEDIDKSANSVLIKNLSRTPSSCSSSLDSIKADGT -> VSSVLNQ FT RMFLNFGFCFVFLNCGYSQILILVSGRQKIIIST (in isoform 4)" FT /evidence="ECO:0000303|PubMed:10980622" FT /id="VSP_018524" FT VAR_SEQ 1860..2342 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:10980622" FT /id="VSP_018525" FT VARIANT 43 FT /note="R -> T (in dbSNP:rs7177192)" FT /evidence="ECO:0000269|PubMed:12087463" FT /id="VAR_026428" FT VARIANT 70 FT /note="T -> A (in dbSNP:rs16970874)" FT /id="VAR_026429" FT VARIANT 113 FT /note="T -> A (in dbSNP:rs12911738)" FT /evidence="ECO:0000269|PubMed:12087463" FT /id="VAR_026430" FT VARIANT 177 FT /note="M -> V (in dbSNP:rs35146555)" FT /id="VAR_061568" FT VARIANT 486 FT /note="A -> S (in dbSNP:rs2412541)" FT /evidence="ECO:0000269|PubMed:10980622, FT ECO:0000269|PubMed:12087463" FT /id="VAR_026431" FT VARIANT 598 FT /note="M -> T (in dbSNP:rs11858113)" FT /evidence="ECO:0000269|PubMed:10980622, FT ECO:0000269|PubMed:12087463, ECO:0000269|PubMed:12618768, FT ECO:0000269|PubMed:18987736" FT /id="VAR_054342" FT VARIANT 936 FT /note="R -> G (in dbSNP:rs8040502)" FT /evidence="ECO:0000269|PubMed:10980622, FT ECO:0000269|PubMed:12087463, ECO:0000269|PubMed:12618768" FT /id="VAR_026432" FT VARIANT 1190 FT /note="L -> V (in dbSNP:rs58614880)" FT /id="VAR_061569" FT VARIANT 1285 FT /note="K -> E (in dbSNP:rs17747633)" FT /evidence="ECO:0000269|PubMed:10980622" FT /id="VAR_026433" FT VARIANT 1473 FT /note="T -> A (in dbSNP:rs16970911)" FT /evidence="ECO:0000269|PubMed:10980622" FT /id="VAR_026434" FT VARIANT 2041 FT /note="M -> I (in MCPH4; may inactivate an exonic splicing FT enhancer and result in abnormal splicing; FT dbSNP:rs763915472)" FT /evidence="ECO:0000269|PubMed:22983954, FT ECO:0000269|PubMed:26626498" FT /id="VAR_069085" FT VARIANT 2338 FT /note="C -> Y (in dbSNP:rs61164860)" FT /id="VAR_061570" FT CONFLICT 37 FT /note="L -> H (in Ref. 3; AAM45143)" FT /evidence="ECO:0000305" FT CONFLICT 1332 FT /note="P -> A (in Ref. 2; BAC05691)" FT /evidence="ECO:0000305" FT CONFLICT 1357 FT /note="N -> H (in Ref. 2; BAC05691)" FT /evidence="ECO:0000305" FT CONFLICT 1756 FT /note="N -> Y (in Ref. 2; BAC05691)" FT /evidence="ECO:0000305" FT HELIX 205..211 FT /evidence="ECO:0007829|PDB:4A1G" FT HELIX 241..250 FT /evidence="ECO:0007829|PDB:3SI5" FT HELIX 2123..2130 FT /evidence="ECO:0007829|PDB:4NF9" FT STRAND 2136..2140 FT /evidence="ECO:0007829|PDB:4NFA" FT STRAND 2146..2151 FT /evidence="ECO:0007829|PDB:4NFA" FT STRAND 2154..2162 FT /evidence="ECO:0007829|PDB:4NFA" FT TURN 2168..2170 FT /evidence="ECO:0007829|PDB:4NFA" FT HELIX 2172..2174 FT /evidence="ECO:0007829|PDB:4NF9" FT STRAND 2177..2184 FT /evidence="ECO:0007829|PDB:4NFA" FT TURN 2188..2190 FT /evidence="ECO:0007829|PDB:4NF9" FT HELIX 2193..2210 FT /evidence="ECO:0007829|PDB:4NFA" FT TURN 2213..2215 FT /evidence="ECO:0007829|PDB:4NF9" FT HELIX 2219..2221 FT /evidence="ECO:0007829|PDB:4NF9" FT HELIX 2222..2249 FT /evidence="ECO:0007829|PDB:4NFA" FT HELIX 2250..2253 FT /evidence="ECO:0007829|PDB:4NFA" FT STRAND 2255..2261 FT /evidence="ECO:0007829|PDB:4NFA" FT STRAND 2264..2271 FT /evidence="ECO:0007829|PDB:4NFA" FT TURN 2272..2275 FT /evidence="ECO:0007829|PDB:4NFA" FT STRAND 2276..2283 FT /evidence="ECO:0007829|PDB:4NFA" FT TURN 2286..2289 FT /evidence="ECO:0007829|PDB:4NFA" FT STRAND 2295..2302 FT /evidence="ECO:0007829|PDB:4NFA" FT HELIX 2306..2315 FT /evidence="ECO:0007829|PDB:4NFA" FT HELIX 2322..2334 FT /evidence="ECO:0007829|PDB:4NFA" SQ SEQUENCE 2342 AA; 265391 MW; 8E29150CA4F5B5C1 CRC64; MDGVSSEANE ENDNIERPVR RRHSSILKPP RSPLQDLRGG NERVQESNAL RNKKNSRRVS FADTIKVFQT ESHMKIVRKS EMEGCSAMVP SQLQLLPPGF KRFSCLSLPE TETGENLLLI QNKKLEDNYC EITGMNTLLS APIHTQMQQK EFSIIEHTRE RKHANDQTVI FSDENQMDLT SSHTVMITKG LLDNPISEKS TKIDTTSFLA NLKLHTEDSR MKKEVNFSVD QNTSSENKID FNDFIKRLKT GKCSAFPDVP DKENFEIPIY SKEPNSASST HQMHVSLKED ENNSNITRLF REKDDGMNFT QCHTANIQTL IPTSSETNSR ESKGNDITIY GNDFMDLTFN HTLQILPATG NFSEIENQTQ NAMDVTTGYG TKASGNKTVF KSKQNTAFQD LSINSADKIH ITRSHIMGAE THIVSQTCNQ DARILAMTPE SIYSNPSIQG CKTVFYSSCN DAMEMTKCLS NMREEKNLLK HDSNYAKMYC NPDAMSSLTE KTIYSGEENM DITKSHTVAI DNQIFKQDQS NVQIAAAPTP EKEMMLQNLM TTSEDGKMNV NCNSVPHVSK ERIQQSLSNP LSISLTDRKT ELLSGENMDL TESHTSNLGS QVPLAAYNLA PESTSESHSQ SKSSSDECEE ITKSRNEPFQ RSDIIAKNSL TDTWNKDKDW VLKILPYLDK DSPQSADCNQ EIATSHNIVY CGGVLDKQIT NRNTVSWEQS LFSTTKPLFS SGQFSMKNHD TAISSHTVKS VLGQNSKLAE PLRKSLSNPT PDYCHDKMII CSEEEQNMDL TKSHTVVIGF GPSELQELGK TNLEHTTGQL TTMNRQIAVK VEKCGKSPIE KSGVLKSNCI MDVLEDESVQ KPKFPKEKQN VKIWGRKSVG GPKIDKTIVF SEDDKNDMDI TKSYTIEINH RPLLEKRDCH LVPLAGTSET ILYTCRQDDM EITRSHTTAL ECKTVSPDEI TTRPMDKTVV FVDNHVELEM TESHTVFIDY QEKERTDRPN FELSQRKSLG TPTVICTPTE ESVFFPGNGE SDRLVANDSQ LTPLEEWSNN RGPVEVADNM ELSKSATCKN IKDVQSPGFL NEPLSSKSQR RKSLKLKNDK TIVFSENHKN DMDITQSCMV EIDNESALED KEDFHLAGAS KTILYSCGQD DMEITRSHTT ALECKTLLPN EIAIRPMDKT VLFTDNYSDL EVTDSHTVFI DCQATEKILE ENPKFGIGKG KNLGVSFPKD NSCVQEIAEK QALAVGNKIV LHTEQKQQLF AATNRTTNEI IKFHSAAMDE KVIGKVVDQA CTLEKAQVES CQLNNRDRRN VDFTSSHATA VCGSSDNYSC LPNVISCTDN LEGSAMLLCD KDEEKANYCP VQNDLAYAND FASEYYLESE GQPLSAPCPL LEKEEVIQTS TKGQLDCVIT LHKDQDLIKD PRNLLANQTL VYSQDLGEMT KLNSKRVSFK LPKDQMKVYV DDIYVIPQPH FSTDQPPLPK KGQSSINKEE VILSKAGNKS LNIIENSSAP ICENKPKILN SEEWFAAACK KELKENIQTT NYNTALDFHS NSDVTKQVIQ THVNAGEAPD PVITSNVPCF HSIKPNLNNL NGKTGEFLAF QTVHLPPLPE QLLELGNKAH NDMHIVQATE IHNINIISSN AKDSRDEENK KSHNGAETTS LPPKTVFKDK VRRCSLGIFL PRLPNKRNCS VTGIDDLEQI PADTTDINHL ETQPVSSKDS GIGSVAGKLN LSPSQYINEE NLPVYPDEIN SSDSINIETE EKALIETYQK EISPYENKMG KTCNSQKRTW VQEEEDIHKE KKIRKNEIKF SDTTQDREIF DHHTEEDIDK SANSVLIKNL SRTPSSCSSS LDSIKADGTS LDFSTYRSSQ MESQFLRDTI CEESLREKLQ DGRITIREFF ILLQVHILIQ KPRQSNLPGN FTVNTPPTPE DLMLSQYVYR PKIQIYREDC EARRQKIEEL KLSASNQDKL LVDINKNLWE KMRHCSDKEL KAFGIYLNKI KSCFTKMTKV FTHQGKVALY GKLVQSAQNE REKLQIKIDE MDKILKKIDN CLTEMETETK NLEDEEKNNP VEEWDSEMRA AEKELEQLKT EEEELQRNLL ELEVQKEQTL AQIDFMQKQR NRTEELLDQL SLSEWDVVEW SDDQAVFTFV YDTIQLTITF EESVVGFPFL DKRYRKIVDV NFQSLLDEDQ APPSSLLVHK LIFQYVEEKE SWKKTCTTQH QLPKMLEEFS LVVHHCRLLG EEIEYLKRWG PNYNLMNIDI NNNELRLLFS SSAAFAKFEI TLFLSAYYPS VPLPSTIQNH VGNTSQDDIA TILSKVPLEN NYLKNVVKQI YQDLFQDCHF YH //